A. Field of Invention
This invention pertains to a system for delivering neuromuscular blocking agents (NMBA) with an infusion pump. The system uses a model of the NMBA's pharmacokinetics and pharmacodynamics and quantatitive input from a clinician to adjust the infusion delivery rate of the NMBA in order to control the level of muscle paralysis while the infusion is in progress.
B. Description of the Prior Art
Neuromuscular blocking agents are routinely given during a surgical procedure by an anesthesia clinician for the purpose of providing near complete muscle paralysis during surgery. The anesthesia clinician typically creates total muscle paralysis at the start of a surgical procedure while the patient is being intubated and the initial incision is made. During the remainder of the surgical procedure, preferably the patient is under a profound but not total level of muscle paralysis to blunt any involuntary movement. By maintaining a near paralysis state with the NMBA, the clinician can easily reverse the paralysis with pharmacologic agents at any time during the procedure. If the patient is in a state of total paralysis, the clinician's ability to reverse the NMBA's effects are delayed and highly unpredictable.
To accomplish this clinical paralysis goal, the anesthesia clinician typically gives a large loading dose of the NMBA at the start of the procedure to achieve total paralysis. As this initial dose begins to wear off, the clinician then supplements the initial dose with either intermittent small bolus doses or with a continuous infusion. The level of muscle paralysis of the patient is monitored regularly using a nerve stimulator. The nerve stimulator activates a muscle and the clinician monitors manually or with instrumentation, the response to the stimulation in order to assess the degree of paralysis obtained. One method of monitoring the degree of paralysis is with a technique referred to as train-of-four (TOF). In this technique, the muscle is first stimulated with four rapid pulses. The degree of paralysis is then determined by counting the number of times the muscle twitches and the relative intensity if the twitch strength with respect to a standardized reference level. The clinical goal is to produce a relatively constant level of muscle paralysis during the procedure. Since the level of paralysis can be assessed by the clinician during the course of the procedure, feedback is available to give a indication of how well this goal is being met.
Previous studies have shown that with the newer, fast acting short duration muscle relaxants that are commonly used today, clinicians can maintain a desired constant level of paralysis better with continuous infusion than with intermittent small bolus injections. Though both techniques exhibited deviations from the desired paralysis level, the infusion group attained the desired level more often and required less manipulation by the clinician. Because the desired clinical effect, that is, muscle paralysis can be quantatitively measured with instrumentation, a complete automated NMBA delivery system was suggested whereby the clinician would specify the desired level of muscle paralysis and the infusion pump, through direct feedback of the level of paralysis, would modulate the infusion delivery rate until the desired level of paralysis was obtained. This approach has the advantage of allowing the clinician to merely specify a set point for the therapeutic goal while the device takes over control for achieving and maintaining the goal. The system produced accurate and consistent levels of muscle paralysis but was too cumbersome and expensive to be clinically useful. Moreover, it may not be desirable for the clinician to be left with the task of merely monitoring the automated delivery system.